Emmetropization is the regulatory process that normally matches the optical power of the eye to its length, so that objects can be focused on the retina. Abnormalities can cause myopia (shortsightedness), in which the eye grows too long for its optical power, leading to sight-threatening complications. Refractive surgery that overcorrects myopia may lead to renewed eye growth, as may certain lighting conditions. Near-epidemic prevalence of myopia in several populations makes it critical and timely to understand the determinants of emmetropization, without which effective treatments are unlikely. Studies: The chick eye has proven to be an effective experimental model for emmetropization: many optical, surgical and pharmacological manipulations can be performed, with time and cost effectiveness, and results generalize well to mammals and primates. Our recent studies in the chick used optic nerve section (ONS) to dissociate retina and brain, and suggested that emmetropization is largely controlled locally, by the retina. Emmetropization with ONS is abnormal. We ask whether this is due to cell loss and retinal rewiring, which are side effects of ONS. Aim 1 (Role of inner retinal cells in emmetropization): We will (a) dissociate retina and brain with a ganglion cell toxin that spares certain fibers destroyed by ONS, (b) use molecular markers to test if ONS causes loss of glucagonergic amacrine cells, and (c) use growth factors to protect ganglion cells in ONS eyes. Visual stimuli are well known to affect posterior segment growth. What determines corneal growth? Aim 2 (Role of the retina in anterior segment growth): We will (a) measure effects of continuous light on corneal flattening, and consequent posterior chamber growth, (b) use radial keratotomy to control for effects of non-visually induced corneal flattening, and (c) measure intersegmental fluid exchange as a potential conduit for retinal factors that control corneal growth. It is still not known how the retina distinguishes the sign of a defocused image. Aim 3 (Decoding defocus in emmetropization): We will manipulate defocus cues with (a) reverse chromatic aberration lenses, (b) blue and red monochromatic rearing, and (c) optical control of object distance, spatial frequency, contrast, and monochromatic aberrations. Reduced retinal acuity may explain the high refractive errors in congenital outer retinal pathologies. Aim 4 (Retinal acuity & emmetropization): We will study in 3 low-acuity preparations: (a) albino chicks, (b) normal chicks reared in UV light, and (c) normal chicks reared in dim light.